The picture of a fixed pathway for nociceptive transmission has long since been abandoned. Rather, nociceptive pathways are highly dynamic or 'plastic', subject to both short- and long-term modulation in response to changes in the periphery. The goal of thin proposal is to increase our understanding of synaptic plasticity at the first nociceptive synapse (between primary afferents and spinal dorsal horn neurons) in response to peripheral nerve injury and to understand how this plasticity leads to the generation of neuropathic pain. Electrophysiological and immunohistochemical techniques will be utilized to determine whether enhanced dorsal horn neuron excitability following peripheral nerve injury results from a loss of inhibitory neurotransmission via GABAergic or glycinergic interneurons. Functional changes that follow injury-induced disinhibition will be examined using phosphorylation of extracellular signal-regulated kinases (ERK1/ERK2) as a marker of neuronal activation. The elucidation of cellular mechanisms in the dorsal horn of the spinal cord that lead to the development of neuropathic pain may provide new opportunities for rational therapeutic intervention.